There are two areas of emphasis in this proposal. The first emphasis is to develop the methodology to perform clinical trails for individuals who are at risk for neurodegenerative diseases. With genetic advances in the major neurodegenerative diseases, it is increasingly possible to identify individuals who are still healthy but who are at a high risk of a neurodegenerative disease. Using the model of Huntington s disease, the research proposal outlines the key initial steps in developing the methodology for clinical trials to prevent or delay the onset of illness. These initial steps include identifying research subject recruitment strategies, identifying methods to clearly define the onset of illness (phenoconversion), reliably identifying this event across investigative sites, and developing outcome measures that can efficiently assess the impact of prevention or delay of illness. An observational study of individuals at risk for HD is proposed to address these issues. The second emphasis of this proposal is mentoring junior faculty committed to patient-oriented research. The central hypothesis of the mentoring plan is that training and mentoring in patient- oriented research must extend beyond the fellowship period to include junior faculty. The structure and emphasis for junior faculty must be different than for fellows and a core curriculum as well as a individual mentoring relationship are proposed. The latter relationship is focused on assisting a junior faculty member in developing novel areas of interest in ongoing research in an effort to develop hypothesis-driven research that can be competitive for peer-reviewed support.